- Iron-Catalyzed Amination of Strong Aliphatic C(sp3)-H Bonds
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A concept for intramolecular denitrogenative C(sp3)-H amination of 1,2,3,4-tetrazoles bearing unactivated primary, secondary, and tertiary C-H bonds is discovered. This catalytic amination follows an unprecedented metalloradical activation mechanism. The utility of the method is showcased with the short synthesis of a bioactive molecule. Moreover, an initial effort has been embarked on for the enantioselective C(sp3)-H amination through the catalyst design. Collectively, this study underlines the development of C(sp3)-H bond functionalization chemistry that should find wide application in the context of drug discovery and natural product synthesis.
- Das, Sandip Kumar,Roy, Satyajit,Khatua, Hillol,Chattopadhyay, Buddhadeb
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p. 16211 - 16217
(2020/10/26)
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- BICYCLIC HYDROXAMIC ACIDS USEFUL AS INHIBITORS OF MAMMALIAN HISTONE DEACETYLASE ACTIVITY
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A compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof. The compound is an inhibitor of a histone deacetylase, and as such is useful in terepy, e.g. in the treatment of autoimmune disorders, mental disorders, neurodegenerative disorders, and hyperproliferative disorders.
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Page/Page column 107
(2017/07/14)
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- OXADIAZOLE MODULATORS OF S1P METHODS OF MAKING AND USING
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The invention is directed to Compounds of Formula (I): wherein each variable is defined herein, as well as methods of making and using the compounds as agonists of S1P1 and/or S1P5 for instance for treating graft versus host disease and autoimmune diseases.
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Paragraph 0183
(2017/01/23)
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- PYRAZOLYL-SUBSTITUTED PYRIDONE COMPOUNDS AS SERINE PROTEASE INHIBITORS
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There are provided inter alia pyrazolyl-substituted pyridone compounds, which exhibit biological activity, e.g., inhibitory action, against serine proteases, including thrombin and various kallikreins. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing certain diseases or disorders, which disease or disorder is amenable to treatment or prevention by the inhibition of serine proteases, including thrombin and various kallikreins.
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Paragraph 00275-00276
(2016/04/09)
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- Design, Synthesis, and Evaluation of Novel Auxin Mimic Herbicides
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Due to the key roles of auxins as master regulators of plant growth, there is considerable interest in the development of compounds with auxin-like properties for growth management and weed control applications. Herein, we describe the design and multiste
- Do-Thanh, Chi-Linh,Vargas, Jose J.,Thomas, Joseph W.,Armel, Gregory R.,Best, Michael D.
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p. 3533 - 3537
(2016/06/01)
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- Design and structural analysis of aromatic inhibitors of type II dehydroquinase from mycobacterium tuberculosis
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3-Dehydroquinase, the third enzyme in the shikimate pathway, is a potential target for drugs against tuberculosis. Whilst a number of potent inhibitors of the Mycobacterium tuberculosis enzyme based on a 3-dehydroquinate core have been identified, they generally show little or no in vivo activity, and were synthetically complex to prepare. This report describes studies to develop tractable and drug-like aromatic analogues of the most potent inhibitors. A range of carbon-carbon linked biaryl analogues were prepared to investigate the effect of hydrogen bond acceptor and donor patterns on inhibition. These exhibited inhibitory activity in the high-micromolar range. The addition of flexible linkers in the compounds led to the identification of more potent 3-nitrobenzylgallate- and 5-aminoiso-phthalate-based analogues.
- Howard, Nigel I.,Dias, Marcio V.B.,Peyrot, Fabienne,Chen, Liuhong,Schmidt, Marco F.,Blundell, Tom L.,Abell, Chris
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p. 116 - 133
(2015/04/14)
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- 6-alkoxy-5-aryl-3-pyridinecarboxamides, a new series of bioavailable cannabinoid receptor type 1 (CB1) antagonists including peripherally selective compounds
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We identified 6-alkoxy-5-aryl-3-pyridinecarboxamides as potent CB1 receptor antagonists with high selectivity over CB2 receptors. The series was optimized to reduce lipophilicity compared to rimonabant to achieve peripherally active molecules with minimal central effects. Several compounds that showed high plasma exposures in rats were evaluated in vivo to probe the contribution of central vs peripheral CB1 agonism to metabolic improvement. Both rimonabant and 14g, a potent brain penetrant CB1 receptor antagonist, significantly reduced the rate of body weight gain. However, 14h, a molecule with markedly reduced brain exposure, had no significant effect on body weight. PK studies confirmed similarly high exposure of both 14h and 14g in the periphery but 10-fold lower exposure in the brain for 14h. On the basis of these data, which are consistent with reported effects in tissue-specific CB1 receptor KO mice, we conclude that the metabolic benefits of CB1 receptor antagonists are primarily centrally mediated as originally believed.
- R?ver, Stephan,Andjelkovic, Mirjana,Bénardeau, Agnès,Chaput, Evelyne,Guba, Wolfgang,Hebeisen, Paul,Mohr, Susanne,Nettekoven, Matthias,Obst, Ulrike,Richter, Wolfgang F.,Ullmer, Christoph,Waldmeier, Pius,Wright, Matthew B.
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p. 9874 - 9896
(2014/01/17)
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- Development of a safe and economical synthesis of methyl 6-chloro-5-(trifluoromethyl)nicotinate: Trifluoromethylation on kilogram scale
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Reported herein is a safe and economical synthesis of methyl 6-chloro-5-(trifluoromethyl)nicotinate, an intermediate in the synthesis of novel anti-infective agents. The key to this process is the trifluoromethylation of an aryl iodide using an inexpensive methyl chlorodifluoroacetate (MCDFA)/KF/CuI system, with an emphasis on the development work which led to this effective process.
- Mulder, Jason A.,Frutos, Rogelio P.,Patel, Nitinchandra D.,Qu, Bo,Sun, Xiufeng,Tampone, Thomas G.,Gao, Joe,Sarvestani, Max,Eriksson, Magnus C.,Haddad, Nizar,Shen, Sherry,Song, Jinhua J.,Senanayake, Chris H.
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supporting information
p. 940 - 945
(2013/07/26)
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- HYDROXAMIC ACID DERIVATIVES AS GRAM-NEGATIVE ANTIBACTERIAL AGENTS
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The invention relates to chemical compounds of formula (IB): or a salt thereof. In some embodiments, the invention relates to inhibitors of UDP-3-0 — (R-S-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC). In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein and their use in the prevention and/or treatment of Gram- negative bacterial infections.
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Page/Page column 74-75
(2010/09/18)
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- 3-Pyridinecarboxamide derivatives as HDL-cholesterol raising agents
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The present invention relates to a method of raising HDL cholesterol comprising administering to a patient in need thereof a compound of the formula wherein A, G, R1 to R8 and R17 are as defined in the description.
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Page/Page column 28
(2008/06/13)
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- Pyridine-3-carboxamide derivatives as CB1 inverse agonists
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The present invention relates to compounds of the formula wherein X and R1 to R8 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with the modulation of CB1 receptors, such as obesity.
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Page/Page column 19
(2008/06/13)
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- PYRIDYL AND PHENYL SUBSTITUTED PIPERAZINE-PIPERIDINES WITH CXCR3 ANTAGONIST ACTIVITY
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The present application discloses a compound, or enantiomers, stereoisomers, rotamers, tautomers, racemates or prodrug of said compound, or pharmaceutically acceptable salts, solvates or esters of said compound, or of said prodrug, said compound having the general structure shown in Formula 1: and the pharmaceutically acceptable salts, solvates and esters thereof. Also disclosed is a method of treating chemokine mediated diseases, such as, palliative therapy, curative therapy, prophylactic therapy of certain diseases and conditions such as inflammatory diseases (non limiting example(s) include, psoriasis), autoimmune diseases (non limiting example(s) include, rheumatoid arthritis, multiple sclerosis), graft rejection (non limiting example(s) include, allograft rejection, xenograft rejection), infectious diseases (e.g , tuberculoid leprosy), fixed drug eruptions, cutaneous delayed-type hypersensitivity responses, ophthalmic inflammation, type I diabetes, viral meningitis and tumors using a compound of Formula 1.
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Page/Page column 134-135
(2008/06/13)
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- A General Synthesis of 5-Arylnicotinates
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Arylboronic acids have been found to couple efficiently with 5-bromonicotinates to yield 5-arylnicotinates.The reaction is considerably more sensitive to steric inhibition in the arylboronic acid component than in the pyridyl bromide 4.The dianion salt of the boronic acid is implicated as the reactive intermediate responsible for the facile coupling reaction.Pure arylboronic acids are best prepared by using triisopropyl borate as the transmetalating agent.
- Thompson, Wayne J.,Gaudino, John
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p. 5237 - 5243
(2007/10/02)
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- Some Methyl 2,5- and 5,6-Dihalonicotinates
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The preparation of the methyl esters of eight dihalonicotinic acids is described.The esters were synthesized either by the methanolysis of their respective acid chlorides or by treatment of the appropriate acid with diazomethane in ether.Experimental and spectral data for the methyl dihalonicotinates are presented.
- Setliff, Frank L.,Hule, W. Reeves
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p. 332 - 333
(2007/10/02)
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